The goals of the proposed studies are to determine if HNF4 is essential for gastrointestinal development, if HNF4 is a central regulator of gastrointestinal gene expression, and if HNF4 controls gene expression by modulating the receptivity of promoters/enhancers to transcriptional activators. Previous studies have shown that HNF4 is a key mediator of gene expression in the liver and that its elimination in the liver blocks hepatocyte differentiation. Cre-loxP technology will be used to conditionally remove Hnf4 from the epithelial cells of the mouse gastrointestinal tract during embryogenesis. The effect of loss of HNF4 in the duodenum, the jejunum and ileum, and the transverse colon will be examined using a combination of histological, immunohistological, and molecular techniques. Gene arrays will be used to identify genes whose expression is dependent upon HNF4 in the gut. Chromatin immunoprecipitation analyses will be used to identify changes in the set of factors bound to gut-specific promoters/enhancers when HNF4 is eliminated from gut epithelial cells. By understanding how this transcription factor functions in the gut, greater insight into the fundamental molecular processes underlying gut development wilt be gained.